| Project/Area Number |
07670262
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | KAWASAKI MEDICAL SCHOOL |
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Principal Investigator |
SADAHIRA Yoshito Kawasaki Med.Sch., Pathology, assistant professor, 医学部, 講師 (30178694)
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| Co-Investigator(Kenkyū-buntansha) |
YASUDA Tatsuji Okayama Univ.Sch.of Med., Professor, 医学部, 教授 (30092357)
WADA Hideho Kawasaki Med.Sch., Hematology, assistant professor, 医学部, 講師 (70191830)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Macrophage / Erythropoiesis / Liposome / Erythropoetin / Spleen / Liver / 肝臓 / マウス / 造血環境 / エリスロポエチン / C-kit ligand / 造血微小環境 |
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| Research Abstract |
In the hematopoietic tissues, erythroid cells closely associate with resident macrophages, forming erythroblastic islands via adhesion molecules. To elucidate the role of macrophages in erythropoiesis, we selectively abrogated resident macrophages of splenic red pulp and liver of phlebotomized mice, by injection with dichrolomethylene-bisphosphonate encapsulated in multilamellar liposomes (C12MDP-liposomes). In the spleen, no erythropoietic activity occurred until 5 days after the treatment. The colony assay revealed that the erythroid suppression occurred at the level of CFU-E.The splenic erythropoietic activity gradually developed from day 6 after the treatment, when F4/80^+ macrophages began to appear in the red pulp. In contrast to the splenic response, extramedullary erythropoiesis occurred in the liver even while F4/80^+ macrophages (Kupffer cells) were eliminated by injection of C12MDP-liposomes. RT-PCR study demonstrated no expression of erythropoietin (EPO) in the liver, spleen, and bone marrow both of the control phlebotomized mice and the phlebotomized mice injected with C12MDP-liposomes. EPO expression of the kidney was enhanced by phlebotomy, but that was suppressed by the injection of C12MDP-liposomes. Injection of recombinant human EPO (rh-EPO) restored splenic erythropoiesis partially and enhanced hepatic erythropoiesis. Thus, poor erythropoietic response in spleen of the phlebotomized mice injected with C12MDP-liposomes might be induced by low erythropoietin production of the kidney and abrogation of macrophages.
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